Coenzyme Q is an essential component widely distributed in living organisms from bacterium to mammal, and is known as a constituent component of an electron transport system of mitochondria in a living cell. Coenzyme Q includes an oxidized type and a reduced type. It repeats oxidization and reduction in mitochondria, thereby functioning as a transduction component in the electron transport system, and reduced coenzyme Q is known to have an antioxidant action. In human, coenzyme Q10, which is a coenzyme Q having a side chain with 10 repeat units, is the main component, and generally, about 40-90% thereof is a reduced type in the living body. The physiological action of coenzyme Q10 includes activation of energy production by mitochondria-activating action, activation of cardiac function, cellular membrane stabilization effect, cell protection effect by antioxidant action and the like.
Of the coenzyme Q10, oxidized coenzyme Q10 is used as a health food in Europe and the United States and as a drug for congestive heart failure in Japan. In recent years, it is also used as a food with nutrient function claims in Japan. Particularly, products of oxidized coenzyme Q10 contained in a soft capsule have been mainly used in the fields of health food and food with nutrient function claims. On the other hand, reduced coenzyme Q10 has not attracted much attention heretofore. In recent years, however, it has been reported to be more effective than oxidized coenzyme Q10 in various applications. For example, a composition containing reduced coenzyme Q10 has been reported to be superior to conventional oxidized coenzyme Q10 alone in the oral absorbability (patent document 1).
The bulk powders of coenzyme Q10, which may be reduced coenzyme Q10, oxidized coenzyme Q10 or a mixture of them, can be obtained, for example, by producing a crude purification product of coenzyme Q10 by a method such as synthesis, fermentation, extraction from naturally occurring substances and the like, concentrating a coenzyme Q10 fraction in an outflow fluid by chromatography, and crystallizing the concentrate by crystal precipitation. However, the thus-obtained bulk powder of coenzyme Q10 takes the form of an ultrafine plate crystal or capillary crystal, which may be stirred up as dust during handling of the powder or stick to a solid surface, causing difficulty in brushing off the entire amount of the powder from a packaging material such as a bag and the like since it attaches thereto. In addition, the powder often agglomerates to form a mass during preservation, thus rendering the handling very difficult, and is known to show markedly poor powder flowability characteristics. Moreover, the powder attaches to bulk powder containers and formulation apparatuses during tableting or capsule filling, thus causing problems in productivity and operability since coenzyme Q10 preparations cannot be formulated smoothly, and the like. Therefore, the development of a granulation or particulate technique capable of improving the powder property of a bulk powder of coenzyme Q10 has been desired. As a granulation or particulate method of oxidized coenzyme Q10, for example, spray-coating of a coating substance while mixing an excipient with oxidized coenzyme Q10 in a fluidized bed apparatus and the like is known (patent document 2).
However, such granulation method has problems in that the content of coenzyme Q10 in the obtained particles unavoidably decreases due to the use of large amounts of an excipient and a coating agent, a special facility is necessary and the like. Even when such granulation method is used, moreover, since the powder flowability characteristics are not sufficient, the powder or particles of the obtained coenzyme Q10 may be ultrafine or a large solid. Thus, the powder and particles are not handled sufficiently easily, and are not satisfactory for application to various uses such as formulation of preparations and the like.
In addition, a granulation method that affords agglomerates of a high content of oxidized coenzyme Q10 crystals by crystallization of oxidized coenzyme Q10 in a system concurrently containing an auxiliary solvent having affinity for oxidized coenzyme Q10 is known (patent document 3). Moreover, a method of improving the flowability during formulation of a preparation of oxidized coenzyme Q10 is also reported (patent document 4).
On the other hand, as a granulation method for reduced coenzyme Q10, a method including crystallizing an oily substance of reduced coenzyme Q10 in water to give reduced coenzyme Q10 (patent document 5) and a method including adding a liquid phase of high concentration of reduced coenzyme Q10 to a poor solvent for granulation (patent document 6) are known. According to these granulation methods, control of the resulting particle size is difficult, and an additional facility such as a tank for preparation of a high concentration liquid phase, a pump for delivery of liquid and the like is necessary.
Among the reports of solidification granulation methods of general liposoluble substances is an embodiment wherein a low melting point substance is melted in water at a temperature not lower than the melting point to give droplets, which are cool-solidified to give granules (patent document 7).    patent document 1: JP-A-10-109933    patent document 2: JP-A-2006-213601    patent document 3: JP-A-2004-130201    patent document 4: JP-A-2004-123594    patent document 5: WO 03/006411    patent document 6: JP-A-2003-89669    patent document 7: JP-A-9-124405